(93c) Rheological Methods for the Bioequivalence Determination of Pharmaceutical Topical Formulations

The purpose of this research was to develop in vitro methods for the assessment of therapeutic equivalence (Q3) of generic and innovator pharmaceutical topical products. Specifically, rheological measurements of four topical formulations that are Q1 and Q2 equivalent were examined to determine if any rheological differences exist. From these measurements, a robust version of the vane method was developed for the determination of yield stress, which can be utilized to quantitatively compare the spreadability of the formulation. Spreadability, the ability to spread under constant force, has been suggested as way to help define the bioequivalence of topical creams.

Initial studies have determined that the vane method technique is feasible in determining rheological differences between the topical formulations provided by the FDA. The data obtained using this technique demonstrated clear differences in the yield stress values between an innovator formulation and a generic equivalent formulation in a quantifiable and reproducible manner. While subjected to the same experimental conditions, a yield stress value of 900.16 +/- 34.90 dyne/cm^2 was obtained for one of the generic formulations and a yield stress value of 581.39 +/- 41.97 dyne/cm^2 was obtained for the innovator formulation. Since yield stress is inversely related to spreadability, the data indicated that the innovator formulation has a higher spreadability compared to the generic formulation. Although improvements are in progress, the vane method has demonstrated the ability to obtain a comparative spreadability assessment for various topical formulations, and this information will prove useful in the determination of Q3 equivalence between generic and innovator topical formulations that are Q1 and Q2 equivalent.

We would like to acknowledge Pradeep M. Sathe, Robert Lionberger, and Lawrence Yu of the Office of Generic Drugs at the Food and Drug Administration for their support and funding of this work. We would also like to thank Michael Bell of the Center for Pharmaceutical Science and Technology at the University of Kentucky for his valuable contributions. Additionally, we would like to acknowledge the National Science Foundation REU program for partially funding this research.